P375: INOTUZUMB OZOGAMICIN PRIOR TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN RELAPSED OR REFRACTORY ACUTE B-LYMPHOBLASTIC LEUKEMIA
Authors: Sabine Kayser, Chiara Sartor, Fabio Giglio, Alessandro Bruno, Jonathan Webster, Patrizia Chiusolo, Francesco Saraceni, Selene Guerzoni, Lara Pochintesta, Erika Borlenghi, Giovanni Marconi, Irene Zacheo, Marco Cerrano, Prassede Salutari, Francesco Restuccia, Mariachiara Abbenante, Mark J Levis, Richard Schlenk, Cristina Papayannidis
Journal: HemaSphere (2023)

Background: Inotuzumab ozogamicin (INO) is a humanized anti-CD22 monoclonal antibody conjugated to calicheamicin, developed as a targeted therapy for B-cell malignancies and favorable efficacy in patients (pts) with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL). At present, allogeneic hematopoietic stem cell transplantation (allo-HCT) is considered a curative option for pts with r/r B-ALL with best outcomes achieved after effective salvage therapy and allo-HCT in complete remission (CR). Veno-occlusive disease, also known as sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of allo-HCT. Furthermore, rates of VOD/SOS may be further increased after pre-treatment with INO. Aims: To characterize a series of r/r B-ALL pts and evaluate outcome after treatment with INO prior to allo-HCT, particularly with respect to risk of VOD/SOS. Methods: We studied 61 r/r pts (median age, 42 years; range, 16-69 years), who were treated with INO between 2016 and 2022 within a compassionate use program (n=7) or in-label after EMA approval (n=54). Fifty (82%) of the 61 pts were heavily pretreated receiving intensive chemotherapy +/- TKI, as well as blinatumomab in 24 (39%), respectively. In addition, allo-HCT at first-line therapy was performed in 11 (18%) pts. All 61 pts were CD22 positive at relapse/progressive disease. Up to 6 INO cycles (1 cycle, n=24; 2 cycles, n=31; 3-4 cycles, n=4; ≥5-6 cycles, n=2) were administered according to the approved regimen. Results: At the time of r/r B-ALL median white blood cell and platelet counts were 5.7/nl (range, 0.2-127/nl) and 104.5/nl (range, 6-400/nl), respectively. Median blast cell count in bone marrow was 36% (range, 0-98%). Twenty-two (36%) pts were female; ECOG was 0 in 60% and 1 or 2 in 40%. Cytogenetic analysis at the time of r/r ALL was available in 27 pts (44%). Eight pts displayed a t(9;22), 10 had a normal karyotype, 4 were complex and 5 had other abnormalities. Fourty-two (75%) of 56 evaluated pts achieved CR after the first INO cycle. Prior to allo-HCT, 52 (85%) of 61 pts achieved CR, 4 (7%) a partial remission, 4 (7%) were refractory and one (1%) with CR after INO relapsed directly before allo-HCT. Median follow-up was 30.5 months (95%-CI, 25.7-41.6) and median overall survival (OS) measured from start of INO was 12.2 months (95%-CI, 7.59-37.1 months). One- and two-years OS rates were 50% (95%-CI, 39-65%) and 37.5% (95%-CI, 26-53%), respectively. VOD/SOS after allo-HCT occurred in 17 (28%) pts. Of those, 9 (53%) pts died due to VOD and multi-organ failure. One had received 5 INO cycles, all others ≤2 INO cycles prior to allo-HCT. In univariable analyses risk factors for VOD/SOS were allo-HCT during first-line therapy (P=0.06) as well as time between last INO and allo-HCT below 60 days (P=0.06). In addition, multivariable models revealed a negative impact of pretreatment with blinatumomab (P=0.05) and allo-HCT during first-line therapy (P=0.03). Relapse/progressive disease occurred in 14 (23%) pts. Of those, only two pts are still alive, all others succumbed of their disease. Cumulative incidences of relapse/progression and death after 20 months were 33% (standard error, (SE) 4.2%) and 38% (SE, 4.3%), respectively. Sixteen (26%) pts died in remission and 22 (36%) pts are in ongoing CR. Summary/Conclusion: This outcome analysis demonstrates that treatment with INO is an effective approach with successful bridge-to-transplant. However, risk of VOD/SOS is high, necessitating continuous monitoring and recognition of VOD/SOS risk factors. Keywords: Allogeneic hematopoietic stem cell transplant, Acute lymphoblastic leukemia, Monoclonal antibody, Clinical outcome